Keywords
Chromosomal copy number variation
Chromosomes 1 and 3
Chromosome 4
Chromosome 7
Chromosome 15
Prenatal diagnosis
Submitted : 2024-11-21
Accepted : 2024-12-06
Published : 2024-12-21
Abstract
Objective: To analyze the clinical value of non-invasive prenatal testing (NIPT) in detecting chromosomal copy number variations (CNVs) and to explore the relationship between gene expression and clinical manifestations of chromosomal copy number variations. Methods: 3551 naturally conceived singleton pregnant women who underwent NIPT were included in this study. The NIPT revealed abnormalities other than sex chromosome abnormalities and trisomy 13, 18, and 21. Pregnant women with chromosome copy number variations underwent genetic counseling and prenatal ultrasound examination. Interventional prenatal diagnosis and chromosome microarray analysis (CMA) were performed. The clinical phenotypes and pregnancy outcomes of different prenatal diagnoses were analyzed. Additionally, a followup was conducted by telephone to track fetal development after birth, at six months, and one year post-birth. Results: A total of 53 cases among 3551 cases showed chromosomal copy number variation. Interventional prenatal diagnosis was performed in 36 cases: 27 cases were negative and 8 were consistent with the NIPT test results. This indicates that NIPT’s positive predictive value (PPV) in CNVs is 22.22%. Conclusion: NIPT has certain clinical significance in screening chromosome copy number variations and is expected to become a routine screening for chromosomal microdeletions and microduplications. However, further interventional prenatal diagnosis is still needed to identify fetal CNVs.
References
Wang Z, Guo Q, Zhou Y, 2016, Current Status and Prospects of Genetic Testing for Chromosomal Microdeletion and Microduplication Syndrome. Chinese Journal of Laboratory Medicine, 39(06): 407–409.
Wapner RJ, Martin CL, Levy B, et al., 2012, Chromosomal Microarray Versus Karyotyping for Prenatal Diagnosis. New Engl J Med, 367(23): 2175–2184.
Liang D, Cram DS, Tan H, et al., 2019, Clinical Utility of Noninvasive Prenatal Screening for Expanded Chromosome Disease Syndromes. Genet Med, 21(9): 1998–2006.
Norton ME, Jacobsson B, Swamy GK, et al., 2015, Cell-Free DNA Analysis for Noninvasive Examination of Trisomy. N Engl J Med, 372(17): 1589–1597.
Malcher C, Yamamotog L, Burnham P, et al., 2018, Development of a Comprehensive Noninvasive Prenatal Test. GenetMol Biol, 41(3): 545–554.
Tan L, Huang T, Li Q, et al., 2021, Application of Non-Invasive Prenatal Testing Technology in Fetal Chromosome Copy Number Variation. Journal of Practical Medicine, 37(22): 2934–2938.
Hong S, Tan M, Wei H, et al., 2023, Analysis of the Positive Predictive Value of NIPT in Copy Number Variation Screening. Chinese Journal of Eugenics and Genetics, 31(04): 804–810.
Pang Y, Wang C, Tang J, et al., 2021, Clinical Application of Noninvasive Prenatal Testing in Detecting Fetal Chromosomal Diseases. Mol Cytogenet, 14(1): 31.
Yang J, Wu J, Peng H, et al., 2021, Performances of NIPT for Copy Number Variations at Different Sequencing Depths Using the Semiconductor Sequencing Platform. Hum Genomics, 15: 41.
Zhao C, Tynan J, Ehrich M, et al., 2015, Detection of Fetal Subchromosomal Abnormalities by Sequencing Circulating Cell-Free DNA from Maternal Plasma. Clin Chem, 61: 608–616.
Haldeman-Englert CR, Jewett T, 2015, 1q21.1 Recurrent Microdeletion. GeneReviews, 8: 93–97.
Mefford H, Hulten M, 2014, 1q21.1 Microdeletions. Unique, 16: 359.
Riddell JVB, Houle A, Franc-Guimond J, et al., 2015, Prenatal Vesico-Allantoic Cyst Outcome — A Spectrum from Patent Urachus to Bladder Exstrophy. Prenat. Diagn., 35: 1342– 1346. https://www.doi.org/10.1002/pd.4702
Fu W, Zhuang J, Wang Y, et al., 2022, Clinical Phenotype and Genetic Analysis of 1q21.1 Microdeletion/Microduplication Fetuses. Progress in Modern Obstetrics and Gynecology, 31(12): 929–933. https://www.doi.org/10.13283/j.cnki.xdfckjz.2022.12.008
Lu G, (ed) 2002 Prenatal Genetic Disease Diagnosis (1st Edition), Guangdong Science and Technology Press, Guangzhou.
Wang W, Hu C, Bi X, et al., 2018, Analysis of 10 Patients with Duplications of 15q11q13 Region and Autism Features. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 35(1): 23–28.